Exosomal Thomsen-Friedenreich Glycoantigen: A New Liquid Biopsy Biomarker for Lung and Breast Cancer Diagnosis.

Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis and management. Many exosome cargos, including proteins, RNAs and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy. However, carbohydrates, an important type of biomolecules, have not yet been explored for this purpose. In this study, we reported a new exosomal carbohydrate biomarker, i.e., alpha-linked Thomsen-Friedenreich glycoantigen (TF-Ag-α; Galß1-3GalNAc alpha). To transform our discovery for clinical applications, we developed a surface plasmon resonance (SPR)-based assay which utilized a unique monoclonal antibody, JAA-F11, with high specificity to TF-Ag-α to measure the levels of exosomal TF-Ag-α in blood. To our knowledge, we are the first to demonstrate that exosomes carry TF-Ag-α. We detected exosomal TF-Ag-α in as low as 10 µL serum samples from cancer patients but in contrast, levels were negligible from normal controls. With a total of 233 cancer patients and normal controls, we showed that exosomal TF-Ag-α detected lung cancer (n=60) and breast cancer (n=95) from normal controls (n=78) with ≥95% and ≥97% accuracy, respectively. These results demonstrated that exosomal TF-Ag-α is a potential liquid biopsy biomarker for cancer diagnosis.

Sex-based Differences in the Lung Immune Microenvironment Are Associated with an Increased Risk of Lung Cancer in Women.

OBJECTIVE: Lung cancer remains a major cause of mortality worldwide, necessitating further understanding of carcinogenesis and its driving factors, including those impacted by sex-dependent variables. We hypothesized that sex-specific lung immune composition may contribute to a greater risk of lung cancer in females. METHODS: Data from 1056 lung cancer screenings were examined for an association between sex and lung cancer risk using time-to-event analyses. Immune profiling by flow cytometry was performed on male and female lungs of three independent mouse models: non-tumor bearing, K-ras mutated, and urethane-exposed carcinogenic. A comparable analysis was performed on human bronchoalveolar lavage samples (n = 81) from lung cancer patients. RESULTS: Of the high-risk screening cohort examined, 60 patients (5.7%) developed lung cancer during median follow-up of 43.4 months. Multivariable stepwise modeling retained female sex (hazard ratio 1.56, P < 0.01) and age (P < 0.01) as prognostic indicators for lung cancer development. Female lung immune profiles in patients included T cell phenotypes consistent with exhaustion (e.g., higher proportions of PD-1+ Ki67-; P = 0.02), an expanded pool of regulatory T cells (P = 0.03), reduced effector T cell frequencies (P = 0.008), and enhancements in suppressive myeloid populations (P = 0.02) versus males, and this is recapitulated in mouse studies. CONCLUSIONS: Female smokers display higher risk for lung cancer. In murine models and humans, female sex is associated with robust immunosuppression within the lung. Further examination of this link will be important in developing immune-based approaches to lung cancer interception and their optimal application across the sexes.

Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging.

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.

Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. This study followed a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperformed existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heatmaps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology. It demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.

Improving Guideline-Recommended Colorectal Cancer Screening in a Federally Qualified Health Center (FQHC): Implementing a Patient Navigation and Practice Facilitation Intervention to Promote Health Equity.

BACKGROUND: Colorectal cancer (CRC) screening is effective in the prevention and early detection of cancer. Implementing evidence-based screening guidelines remains a challenge, especially in Federally Qualified Health Centers (FQHCs), where current rates (43%) are lower than national goals (80%), and even lower in populations with limited English proficiency (LEP) who experience increased barriers to care related to systemic inequities. METHODS: This quality improvement (QI) initiative began in 2016, focused on utilizing patient navigation and practice facilitation to addressing systemic inequities and barriers to care to increase CRC screening rates at an urban FQHC, with two clinical locations (the intervention and control sites) serving a diverse population through culturally tailored education and navigation. RESULTS: Between August 2016 and December 2018, CRC screening rates increased significantly from 31% to 59% at the intervention site (p < 0.001), with the most notable change in patients with LEP. Since 2018 through December 2022, navigation and practice facilitation expanded to all clinics, and the overall CRC screening rates continued to increase from 43% to 50%, demonstrating the effectiveness of patient navigation to address systemic inequities. CONCLUSIONS: This multilevel intervention addressed structural inequities and barriers to care by implementing evidence-based guidelines into practice, and combining patient navigation and practice facilitation to successfully increase the CRC screening rates at this FQHC.

The Cancer Screening and Survivorship Program at Roswell Park Comprehensive Cancer Center.

Roswell Park Comprehensive Cancer Center (Roswell) is the only NCI-designated cancer center in New York State outside of the New York City metropolitan area. The Cancer Screening and Survivorship Program combines cancer screening services with survivorship care in a freestanding centralized clinic with providers also dispersed to see survivors in other clinical areas. The aims of the program are to provide comprehensive, patient-centered care to cancer survivors and their families and caregivers by addressing symptoms, supporting wellness, prevention and quality of life, and engaging community primary care providers in a shared-care model. The clinic is led by an onco-generalist, defined as an internal medicine trained physician serving cancer survivor's medical issues from all cancer disease sites. Roswell's Cancer Screening and Survivorship Program growth and development is guided by ongoing research related to patient needs and barriers to care, overall quality of life, health promotion and prevention, as well as education and training to build a more robust cancer survivorship workforce. The cancer center leadership has identified the expansion of cancer survivorship paired with community outreach and engagement, PCP outreach and education, and comprehensive cancer screening services as one of the key strategic areas of growth over the next decade. With the investment in our long-term strategic plan, we expect to continue to grow and serve a broader community of cancer survivors and further our research related to the structure and outcomes of our programmatic activities. IMPLICATIONS FOR CANCER SURVIVORS: This program provides robust whole-person care for cancer survivors and provides an example of successful infrastructure for cancer survivorship.

Immunoprofiling bronchoalveolar lavage cells reveals multifaceted smoking-associated immune dysfunction.

Background: Bronchoalveolar lavage (BAL) is an underutilised tool in the search for pulmonary disease biomarkers. While leukocytes with effector and suppressor function play important roles in airway immunity and tumours, it remains unclear if frequencies and phenotypes of BAL leukocytes can be useful parameters in lung cancer studies and clinical trials. We therefore explored the utility of BAL leukocytes as a source of biomarkers interrogating the impact of smoking, a major lung cancer risk determinant, on pulmonary immunity. Methods: In this "test case" observational study, BAL samples from 119 donors undergoing lung cancer screening and biopsy procedures were evaluated by conventional and spectral flow cytometry to exemplify the comprehensive immune analyses possible with this biospecimen. Proportions of major leukocyte populations and phenotypic markers levels were found. Multivariate linear rank sum analysis considering age, sex, cancer diagnosis and smoking status was performed. Results: Significantly increased frequencies of myeloid-derived suppressor cells and PD-L1-expressing macrophages were found in current and former smokers compared to never-smokers. While cytotoxic CD8 T-cells and conventional CD4 helper T-cell frequencies were significantly reduced in current and former smokers, expression of immune checkpoints PD-1 and LAG-3 as well as Tregs proportions were increased. Lastly, the cellularity, viability and stability of several immune readouts under cryostorage suggested BAL samples are useful for correlative end-points in clinical trials. Conclusions: Smoking is associated with heightened markers of immune dysfunction, readily assayable in BAL, that may reflect a permissive environment for cancer development and progression in the airway.

Simultaneous Detection of Tumor Derived Exosomal Protein-MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis.

Tumor derived exosomes (TEXs) have emerged as promising biomarkers for cancer liquid biopsy. Conventional methods (such as ELISA and qRT-PCR) and emerging biosensing technologies mainly detect a single type of exosomal biomarker due to the distinct properties of different biomolecules. Sensitive detection of two different types of TEX biomarkers, i.e., protein and microRNA combined biomarkers, may greatly improve cancer diagnostic accuracy. We developed an exosome protein microRNA one-stop (Exo-PROS) biosensor that not only selectively captured TEXs but also enabled in situ, simultaneous detection of TEX protein-microRNA pairs via a surface plasmon resonance mechanism. Exo-PROS assay is a fast, reliable, low sample consumption, and user-friendly test. With a total of 175 cancer patients and normal controls, we demonstrated that TEX protein-microRNA pairs measured by Exo-PROS assay detected lung cancer and breast cancer with 99% and 96% accuracy, respectively. Exo-PROS assay also showed superior diagnostic performance to conventional ELISA and qRT-PCR methods. Our results demonstrated that Exo-PROS assay is a potent liquid biopsy assay for cancer diagnosis.

Predictors of Hospital Readmission in Patients Undergoing Creation of an Intestinal Ostomy.

PURPOSE: The purpose of this study was to identify predictors of 30- and 60-day hospital readmission in patients undergoing ileostomy or colostomy creation. DESIGN: A retrospective, cohort study. SAMPLE AND SETTING: The study sample comprised 258 patients who underwent ileostomy or colostomy creation from 2018 to 2021 in a suburban teaching hospital in the northeastern United States. The mean age of participants was 62.8 (SD 15.8) years; half were female and half were male. Slightly more than half 50.3% (n = 130) and 49.2% (n =127) underwent ileostomy surgery. METHODS: Data were abstracted from the electronic medical record and included the following variable categories: demographic factors, ostomy- and surgical-related factors, and ostomy- and surgical-related complications. Study outcome measures were readmission within 30 and 60 days from the index hospital admission discharge date. Predictors of hospital readmission were analyzed using bivariate testing, followed by multivariate analysis. RESULTS: Within 30 days of the index hospitalization, 49 patients were readmitted (19%), and 17 patients were readmitted (6.6%) within 60 days. For readmissions within 30 days, anatomical location of the stoma in the ileum and transverse colon as compared to descending/sigmoid colon stomas emerged as significant predictors (odds ratio [OR] 2.2; P = .036; confidence interval [CI] 1.05-4.85; OR 4.5; P = .036; CI 1.17-18.53, respectively). Within 60 days, length of the index hospitalization from 15 to 21 days as compared to shorter lengths of hospitalization emerged as the only significant predictor at this timeframe (OR 6.62; P = .018, CI 1.37-31.84). CONCLUSIONS: These factors provide a basis for identifying patients at higher risk for hospital readmission following ileostomy or colostomy surgery. For patients at higher risk for readmission following ostomy surgery, heightened surveillance and management in the immediate postoperative period may be necessary to avert potential complications.

Adapting Community Educational Programs During the COVID-19 Pandemic: Comparing the Feasibility and Efficacy of a Lung Cancer Screening Educational Intervention by Mode of Delivery.

Few eligible patients receive lung cancer screening. We developed the Lung AIR (awareness, information, and resources) intervention to increase community education regarding lung cancer screening. The intervention was designed as an in-person group intervention; however, the COVID-19 pandemic necessitated adapting the mode of delivery. In this study we examined intervention feasibility and efficacy overall and by mode of delivery (in-person group vs. one-on-one phone) to understand the impact of adapting community outreach and engagement strategies. Feasibility was examined through participant demographics. Efficacy was measured through pre/post knowledge, attitudes, and beliefs about lung cancer screening, and intention to complete screening. We reached N = 292 participants. Forty percent had a household income below $35,000, 58% had a high school degree or less, 40% were Hispanic, 57% were Black, and 84% reported current or past smoking. One-on-one phone sessions reached participants who were older, had lower incomes, more current smoking, smoked for more years, more cigarettes per day, lower pre-intervention lung cancer screening knowledge, and higher pre-intervention fear and worry. Overall pre/post test scores show significant increases in knowledge, salience, and coherence, and reduced fear and worry. Participants in the one-on-one phone sessions had significantly higher increases in salience and coherence and intention to complete screening compared to participants in the in-person group sessions. The Lung AIR intervention is a feasible and effective community-based educational intervention for lung cancer screening. Findings point to differences in reach and efficacy of the community-based intervention by mode of delivery.

A nurse-delivered intervention to reduce insomnia in cancer survivors: Study protocol for a randomized-controlled trial.

Insomnia has been frequently reported as one of the most burdensome symptoms among cancer survivors. To date, little research exists on strategies to effectively reduce insomnia in cancer survivors, especially in the application of cognitive behavioral therapy for insomnia (CBTI) at the bedside by nurses. The current objective is to determine efficacy and durability of a streamlined, individually delivered version of CBTI, specifically Brief Behavioral Therapy for Insomnia (BBTI) versus a healthy eating attention control, using a large heterogeneous sample of 158 cancer survivors. Study participants will be adults ≥18 years of age; ≥1 month from treatment (except hormones and targeted therapies are acceptable) for stages I through III breast, colorectal, lung or prostate cancers; meet criteria for insomnia defined by Insomnia Severity Index (ISI) >7; screen negative for obstructive sleep apnea <15 events/h; and ability to complete data collection instruments in English. Baseline, and then 1-, 3-, and 12-month objective (i.e., actigraphy) and subjective sleep, mood, and quality of life assessments after the interventions are planned. The primary outcome will be measured with the ISI, a psychometrically-sound instrument used to measure perceived insomnia severity. The results of this trial will demonstrate the application of BBTI in a larger heterogenous sample of cancer survivors for the first time and may lead to implementation strategies that will promote the dissemination and sustainability of this intervention. Clinical trials identifier: http://ClinicalTrials.gov, NCT03810365.

Bacteria communities and water quality parameters in riverine water and sediments near wastewater discharges.

Wastewater treatment plant (WWTP) discharges alter water quality and microbial communities by introducing human-associated bacteria in the environment and by altering microbial communities. To fully understand this impact, it is crucial to study whether WWTP discharges affect water and sediments microbial communities in comparable ways and whether such effects depend on specific environmental variables. Here, we present a dataset investigating the impact of a WWTP on water quality and bacterial communities by comparing samples collected directly from the WWTP outflow to surface waters and sediments at two sites above and two sites below it over a period of five months. When possible, we measured five physicochemical variables (e.g., temperature, turbidity, conductivity, dissolved oxygen, and salinity), four bioindicators (e.g., Escherichia coli, total coliforms, Enterococcus sp., and endotoxins), and two molecular indicators (e.g., intI1's relative abundance, and 16S rRNA gene profiling). Preliminary results suggest that bioindicators correlate with environmental variables and that bacterial communities present in the water tables, sediments, and treated water differ greatly in composition and structure.

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC.

Background: CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC. Methods: Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design. Toxicities were graded according to CTCAE V4.03. Thirteen patients (one unevaluable), the majority with PD-L1 0%, were enrolled into two dose levels of CIMAvax-EGF. Findings: The combination was determined to be safe and tolerable. The recommended phase 2 dose of CIMAvax-EGF was 2.4 mg. Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

RAISE: A Management and Organizational Sustainability Tool for Local Governments to Systematically Self-Evaluate the Effectiveness of Their Programs.

CONTEXT: Many donor-driven public health programs are now seeking evidence for sustainability prior to investment, creating the need for tools to better appraise these capabilities. Assessing the sustainability of programs and interventions at the local level remains a community-wide challenge. PROGRAM: This article presents a new self-assessment tool, the Reflection and Action to Improve Self-reliance and Effectiveness (RAISE) Tool ("the Tool"), modeled after The Challenge Initiative's (TCI) Sustainability Pillars. It describes the evolution of the Tool, explores its structure and applications, demonstrates its data analysis capabilities, and illustrates how it can be used for continuous program self-assessment by local governments, which TCI considers an indicator of program sustainability at the local level. IMPLEMENTATION: Developed in 2019, the Tool has been adapted, adopted, and implemented by 92 local governments across 11 countries. The Challenge Initiative works with these local governments over a minimum of 3 years, providing management and technical coaching on high-impact interventions. Using the Tool, local governments self-assess and evaluate the quality and effectiveness of their activity implementation and identify gaps for improvement. The Tool helps both local governments and TCI track their readiness toward becoming self-reliant and taking ownership of their family planning programs. EVALUATION: As of June 30, 2021, 39 of the 92 local governments reached the final stage of maturity, self-reliance. DISCUSSION: Experts have stated that it can take 15 years for a sustainability assessment tool such as RAISE to be adopted into government policies. After 2 years of using the Tool on a quarterly basis, on average 87.3% of eligible local governments completed the self-assessments, made course corrections, and have taken steps toward program independence. The 39 local governments that successfully progressed to self-reliance continue to use the Tool without TCI's coaching support and have expressed interest in adapting the Tool for other health interventions.

Ultrafast Detection of Exosomal RNAs via Cationic Lipoplex Nanoparticles in a Micromixer Biochip for Cancer Diagnosis.

Exosomes are cell-derived, nanosized extracellular vesicles for intercellular communication. Exosomal RNAs have been shown as one type of promising cancer liquid biopsy biomarkers. Conventional methods to characterize exosomal RNAs such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) are limited by low sensitivity, large sample consumption, time-consuming process, and high cost. Many technologies have been developed to overcome these challenges; however, many hours are still required to complete the assays, especially when exosome lysis and RNA extraction are required. We have developed a microfluidic cationic lipoplex nanoparticles (mCLN) assay that utilizes a micromixer biochip to allow for the effective capture of exosomes by cationic lipoplex nanoparticles and thus enables ultrafast and sensitive exosomal RNA detection for cancer diagnosis. The sensing performance and diagnostic performance of the mCLN assay were investigated using non-small cell lung cancer (NSCLC) as the disease model and exosomal microRNA-21 and TTF-1 mRNA as the biomarkers. The limits of detection of the mCLN assay were 2.06 × 109 and 3.71 × 109 exosomes/mL for microRNA-21 and TTF-1 mRNA, respectively, indicating that the mCLN assay may require as low as 1 µL of serum for exosomal RNA detection. The mCLN assay successfully distinguished NSCLC from normal controls by detecting significantly higher microRNA-21 and TTF-1 mRNA levels in exosomes from both NSCLC patient serum samples and A549 NSCLC cells than those from normal controls and BEAS-2B normal bronchial epithelial cells. Compared with conventional qRT-PCR assay, the mCLN assay showed a higher diagnostic accuracy in lung cancer, required less sample volume (30 vs 100 µL), and consumed much less time (10 min vs 4 h).

Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions.

OBJECTIVE: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features. METHODS: Endobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and PML outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (ie, found in one patient only) and public (ie, found in two or more patients) TCRs was quantified, and the CDR3 sequences were compared with those found in curated databases with known antigen specificities. RESULTS: We detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T cell mediated immune activation (p=4e-4) associated with PML outcome. Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3396 (8.6%) found in more than one sample and 1057 (2.7%) found in two or more patients (ie, public); however, when compared with a public database of CDR3 sequences, 4543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among public TCRs (p<0.001). CONCLUSIONS: Decreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.

Aberrant epithelial polarity cues drive the development of precancerous airway lesions.

Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the conditional deletion of the apical determinant Crumbs3 (Crb3), initiates and sustains precancerous airway pathology. The loss of Crb3 in adult luminal airway epithelium promotes the uncontrolled activation of the transcriptional regulators YAP and TAZ, which stimulate intrinsic signals that promote epithelial cell plasticity and paracrine signals that induce basal-like cell growth. We show that aberrant polarity and YAP/TAZ-regulated gene expression associates with human bronchial precancer pathology and disease progression. Analyses of YAP/TAZ-regulated genes further identified the ERBB receptor ligand Neuregulin-1 (NRG1) as a key transcriptional target and therapeutic targeting of ERBB receptors as a means of preventing and treating precancerous cell growth. Our observations offer important molecular insight into the etiology of LUSC and provides directions for potential interception strategies of lung cancer.

Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center.

Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.